Terminal half-life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database.
extended half-life
factor IX
factor VIII
pharmacokinetics
prophylaxis
standard half-life
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
26
04
2021
received:
19
02
2021
accepted:
11
05
2021
pubmed:
21
5
2021
medline:
10
8
2021
entrez:
20
5
2021
Statut:
ppublish
Résumé
Real-life data on pharmacokinetics of factor (F) VIII/IX concentrates, especially extended half-life (EHL), concentrates in large cohorts of persons with hemophilia are currently lacking. This cross-sectional study aimed to establish reference values for terminal half-life (THL) for FVIII/IX concentrates according to concentrate type, age, blood group and inhibitor history. Data were extracted from the Web-Accessible Population Pharmacokinetics Service database. Groups were compared by nonparametric tests. THL was modelled according to patient characteristics and concentrate type. Infusion data (n = 8022) were collected from 4832 subjects (including 2222 children) with severe hemophilia (age: 1 month-85 years; 89% hemophilia A; 34% using EHL concentrates, 9.8% with history of inhibitors). THL of FVIII-EHL was longer than of FVIII standard half-life (SHL; median 15.1 vs. 11.1 h). FVIII-THL was dependent on age, concentrate type, blood group, and inhibitor history. THL of FIX-EHL was longer than of FIX-SHL (median 106.9 vs. 36.5 h). FIX-THL increased with age until 30 years and remained stable thereafter. FVIII-THL was shorter in subjects with blood group O. THL was decreased by 1.3 h for FVIII and 22 h for FIX in subjects with a positive inhibitor history. We established reference values for FVIII/IX concentrates according to patient characteristics and concentrate type in a large database of hemophilia patients. These reference values may inform clinical practice (e.g., assessment of immune tolerance success), economic implications of procurement processes and value attribution of novel treatments (e.g., mimetics, gene therapy).
Sections du résumé
BACKGROUND
Real-life data on pharmacokinetics of factor (F) VIII/IX concentrates, especially extended half-life (EHL), concentrates in large cohorts of persons with hemophilia are currently lacking.
OBJECTIVES
This cross-sectional study aimed to establish reference values for terminal half-life (THL) for FVIII/IX concentrates according to concentrate type, age, blood group and inhibitor history.
PATIENTS/METHODS
Data were extracted from the Web-Accessible Population Pharmacokinetics Service database. Groups were compared by nonparametric tests. THL was modelled according to patient characteristics and concentrate type.
RESULTS
Infusion data (n = 8022) were collected from 4832 subjects (including 2222 children) with severe hemophilia (age: 1 month-85 years; 89% hemophilia A; 34% using EHL concentrates, 9.8% with history of inhibitors). THL of FVIII-EHL was longer than of FVIII standard half-life (SHL; median 15.1 vs. 11.1 h). FVIII-THL was dependent on age, concentrate type, blood group, and inhibitor history. THL of FIX-EHL was longer than of FIX-SHL (median 106.9 vs. 36.5 h). FIX-THL increased with age until 30 years and remained stable thereafter. FVIII-THL was shorter in subjects with blood group O. THL was decreased by 1.3 h for FVIII and 22 h for FIX in subjects with a positive inhibitor history.
CONCLUSIONS
We established reference values for FVIII/IX concentrates according to patient characteristics and concentrate type in a large database of hemophilia patients. These reference values may inform clinical practice (e.g., assessment of immune tolerance success), economic implications of procurement processes and value attribution of novel treatments (e.g., mimetics, gene therapy).
Identifiants
pubmed: 34013558
doi: 10.1111/jth.15395
pmc: PMC8361743
pii: S1538-7836(22)01856-6
doi:
Substances chimiques
Blood Group Antigens
0
Factor VIII
9001-27-8
Factor IX
9001-28-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1896-1906Informations de copyright
© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.
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